Extracellular peptidase activity tunes motor pattern modulation

We are examining how extracellular peptidase activity sculpts the peptidergic actions of modulatory projection neurons on rhythmically active neuronal circuits, using the pyloric circuit in the stomatogastric ganglion (STG) of the crab Cancer borealis. Neurally released peptides can diffuse long distances to bind to their receptors. Hence, different neurons releasing the same neuropeptide into the same neuropil may reach the same receptor complement. However, extracellular peptidases can limit neuropeptide diffusion and terminate its actions. Distinct versions of the pyloric rhythm are elicited by selective activation of different projection neurons, including those with overlapping sets of cotransmitters. Two of these projection neurons, modulatory commissural neuron 1 (MCN1) and the modulatory proctolin neuron (MPN), contain the neuropeptide proctolin plus GABA. MCN1 also contains Cancer borealis tachykinin-related peptide Ia (CabTRP Ia). CabTRP Ia is not fully responsible for the distinct actions of MCN1 and MPN. Because there is aminopeptidase activity in the STG that terminates proctolin actions, we tested the hypothesis that the differences in the actions of MCN1 and MPN that are not mediated by CabTRP Ia result from the differential actions of aminopeptidase activity on proctolin released from these two projection neurons. We found that the pyloric circuit response to these two projection neurons becomes more similar when this aminopeptidase activity is blocked. This result supports the hypothesis that extracellular peptidase activity enables different projection neurons to use the same neuropeptide transmitter for eliciting distinct outputs from the same neuronal circuit.